The present invention relates to an antibody-producing hybridoma, antibody, and a method of antibody production.
The method for producing monoclonal antibody (hereinafter also abbreviated MoAb) using a hybridoma, developed by Kohler and Milstein, is advantageous in that a monospecific antibody can be obtained in large amounts and stably; it is widely applied to various fields [Kohler, G. and Milstein, C.; Nature, 256, 495 (1975)]. In particular, it has recently been making great contributions to the development of new preventive and therapeutic drugs as well as to the detection and purification of antigens and development of diagnostics.
However, in administering mouse MoAb, a protein foreign to humans, as a preventive and/or therapeutic drug, there is a risk that the therapeutic effect may be attenuated as a result of production of an antibody against mouse MoAb in human bodies; as well, serious allergic reaction may result. Therefore, human MoAb is much more desirable for use as a preventive and/or therapeutic drug, but human MoAb preparation lags far behind mouse MoAb preparation in technical advancement, with only a few successes in actual preparation. Human MoAb is produced using human-human hybridomas, mouse-human hetero hybridomas and Epstein-Barr virus (hereinafter also abbreviated EBV) transformants of human lymphocytes etc. Since the latter two are inferior to the former in stability of antibody production and proliferativity, it is desired that human MoAb be produced using a human-human hybridoma. However, the fusion efficiency in the preparation of human-human hybridomas is generally very low, which considerably retards the development of human MoAb as a pharmaceutical. To overcome this drawback, parental lines have been under development which are excellent in proliferativity and which can be fused with a human lymphocyte at high efficiency; Yamada et al. established the HO-323 cell line [Yamada, K. and Murakami, H.; Fermentation and Industry (in Japanese), 45, 218 (1987)] and Ichimori et al. the TAW-925 cell line [Ichimori, Y., Harada, K., et al.; Biochemical and Biophysical Research Communications, 142, 805 (1987)]. At present, however, there is urgent need for development of a parental line which will yield a human-human hybridoma possessing stable antibody productivity and excellent proliferativity, and which can be fused with a human lymphocyte to prepare said hybridoma at still higher efficiency.
The purpose of the present invention is to provide a human-human hybridoma which produces an antibody stably and which possesses excellent proliferativity, a method of antibody production using said hybridoma, and the antibody produced by said hybridoma.